A typical transdermal drug delivery or wound dressing system comprises a flexible backing on which are applied either as one layer or in spatial separation: a pressure sensitive adhesive, the desired drug, and, particularly in the case of the transdermal systems, a skin-penetration enhancer for the drug. The enhancers useful in transdermal drug delivery applications are well documented and fall into the categories of sulfoxides, alcohols, fatty acids, fatty acid esters, polyols, polyamides, and surfactants.
Historically, the adhesives used for transdermal drug delivery fall into one of three categories: acrylics, silicones and rubbers. Silicone based adhesives have a long history of use on skin because of their purity and low tendency to cause skin irritation. However, their non-polar nature limits the loading of polar drugs into the adhesive and the chemistry renders the composition relatively inflexible. Rubber based adhesives on the other hand are more flexible, but need to be formulated with relatively high amounts tackifiers and plasticizers to provide pressure sensitive properties, and antioxidants to improve stability upon exposure to light (UV). The presence of such high levels of low molecular weight additives leads to skin irritation and presents the danger of the additives penetrating the skin barrier. Rubber based adhesives are also non-polar and thus limit the loading of functional drugs into the adhesive.
In comparison to silicones and rubber adhesives, acrylic adhesives offer a number of advantages: the chemistry is easily manipulated to permit the synthesis of both polar and non-polar adhesives; conventional synthetic techniques can be used; compositions can be tailored to give specific properties without the use of any added ingredients; they are UV stable and can be stored for extended periods of time; and most drugs are more readily soluble in acrylic adhesives than in silicones and rubbers, which allows a higher loading of drug into a smaller patch size and serves to improve patient compliance.
Despite these advantages, acrylic adhesives are highly compatible or soluble in the commonly used skin penetration enhancers compared to the relatively inert silicones and rubbers. This compatibility limits the loading of enhancer and, consequently, the capability of the system to deliver optimum levels of the desired drugs. It also, over time, causes the acrylic adhesive to plasticize to such an extent that it disintegrates with a loss of cohesive and adhesive properties.
Attempts have been made to counteract this dissolution by increasing the level of crosslinking in the adhesive or by grafting polymers, such as polystyrene, with higher Tg values onto the acrylic polymeric chain. However, high crosslinking results in inflexible adhesives, and as the enhancer becomes depleted by absorption into the skin, the presence of the high Tg polystyrene grafts causes a loss in pressure sensitive properties.
In addition to problems with the compositions of the adhesives, the techniques for making the graft and block copolymers with acrylic backbone also present problems. Techniques described in the literature include polymerization of the grafted moiety from a site, such as a hydroxyl group, on the backbone polymer using peroxides as free radical initiators, or the use of macromonomers (as the grafted moiety) with a terminal double bond as a monomer during polymerization. The use of peroxides to initiate a polymerization from sites on the backbone results in uncontrolled grafting in terms of frequency and length of grafts. Uncontrolled grafting produces a polymer with morphologies that do not give optimum cohesion (because of low molecular weight homopolymer formation) or produces low molecular weight grafts that do not provide any reinforcement in the presence of enhancers. The use of macromers during a free radical polymerization is inefficient, results in high residual monomers, and early chain termination because of the large number of terminating sites available on the grafts.
It would be an advantage to provide an adhesive, suitable for use in a wound dressing or transdermal drug delivery system, that maintains its pressure sensitive properties and does not dissolve in the commonly used skin-penetration enhancers over time and through use.
The objects of this invention are to provide a pressure sensitive acrylic polymer with sufficient cohesion and adhesion for use in transdermal drug delivery systems that is insoluble in the commonly used enhancers, and thus will maintain its adhesive and cohesive strength over time.